Elucidating the adaptation and temporal coordination of metabolic pathways using in-silico evolution

0442496 - ÚVGZ 2015 RIV IE eng J - Článek v odborném periodiku
Gottstein, W. - Müller, Stefan - Herzel, H. - Steuer, Ralf
Elucidating the adaptation and temporal coordination of metabolic pathways using in-silico evolution.
Biosystems. Roč. 117, mar (2014), s. 68-76. ISSN 0303-2647. E-ISSN 1872-8324
Grant CEP: GA MŠMT(CZ) EE2.3.20.0256
Institucionální podpora: RVO:67179843
Klíčová slova: evolutionary algorithms * flux-balance analysis * metabolic oscillations * metabolism * systems biology
Kód oboru RIV: EI - Biotechnologie a bionika
Impakt faktor: 1.548, rok: 2014

Cellular metabolism, the interconversion of small molecules by chemical reactions, is a tightly coordinated process that requires integration of diverse environmental and intracellular cues. While for many organisms the topology of the network of metabolic reactions is increasingly known, the regulatory principles that shape the network's adaptation to diverse and changing environments remain largely elusive. To investigate the principles of metabolic adaptation and regulation in metabolic pathways, we propose a computational approach based on in-silico evolution. Rather than analyzing existing regulatory schemes, we let a population of minimal, prototypical metabolic cells evolve rate constants and appropriate regulatory schemes that allow for optimal growth in static and fluctuating environments. Applying our approach to a small, but already sufficiently complex, minimal system reveals intricate transitions between metabolic modes. These results have implications for trade-offs in resource allocation. Going from static to varying environments, we show that for fluctuating nutrient availability, active metabolic regulation results in a significantly increased overall rate of metabolism.
Trvalý link: http://hdl.handle.net/11104/0245322